Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians

Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians John C. Chambers 1 , Weihua Zhang 1 , Delilah Zabaneh 1 , Joban Sehmi 2 , Piyush Jain 2 , Mark I. McCarthy 3 , Philippe Froguel 4 , 5 , Aimo Ruokonen 6 , David Balding 1 , Marjo-Riitta Jarvelin 1 , 7 , James Scott 2 , Paul Elliott 1 and Jaspal S. Kooner 2 1 Department of Epidemiology and Public Health, Imperial College London, London, U.K.; 2 National Heart and Lung Institute, Imperial College London, London, U.K.; 3 Oxford Centre for Diabetes, Endocrinology and Metabolism and Oxford National Institute for Health Research, Biomedical Research Centre, Oxford, U.K.; 4 Section of Genomic Medicine, Imperial College London, London, U.K., and the Centre National de la Recherche Scientifique, 8090-Institute of Biology, Pasteur Institute, Lille, France; 5 UMR 8090-Institute of Biology, Pasteur Institute, Lille, France; 6 Department of Clinical Sciences/Clinical Chemistry, University Hospital Oulu, Oulu, Finland; 7 Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland, and Department of Child and Adolescent Health, National Institute of Health and Welfare, Helsinki, Finland. Corresponding author: Jaspal S. Kooner, j.kooner{at}imperial.ac.uk . Abstract OBJECTIVE Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. RESEARCH DESIGN AND METHODS We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. RESULTS We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 × 10 −8 , all near melatonin receptor MTNR1B . The most closely associated was rs2166706 (combined P = 2.1 × 10 −9 ), which is in moderate linkage disequilibrium with rs1387153 ( r 2 = 0.60) and rs10830963 ( r 2 = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively ( P